Sudden changes in the environment can disrupt cellular processes. Cells possess damage-control mechanisms to cope with these environmental stresses, and thus exhibit some tolerance to such external insults. But cells can also be quite vulnerable; environmental stress causes cellular defects that are the basis of certain neurodegenerative diseases and aging. In the context of embryonic development, cells must execute a programmed set of rapid cell divisions, which are largely dependent on the action of cytoskeletal proteins whose structures and functions are highly sensitive to environmental stress. How do embryos maintain cellular function and normal development in the face of environmental stress? The goal of this research program is to identify the molecular and cellular mechanisms that underlie tolerance to environmental stress in vivo in Drosophila melanogaster embryos. The training will take an innovative approach by emphasizing the use of techniques in microscopy and developmental genetics to define and manipulate embryonic thermal tolerance. The embryonic thermal stress phenotype will be dissected at cellular resolution (1) across multiple genotypes, (2) in embryos with disrupted expression of candidate proteins that stabilize the cytoskeleton, and (3) among natural isolates of wild Drosophila from distinct thermal environments. This research will have a broad impact by contributing to our basic knowledge of how cells respond to environmental stress and by identifying candidate pathways that are the basis of stress tolerance at both the cellular and whole-organism levels. PUBLIC HEALTH RELEVANCE: The ability for cells to respond to environmental stress is fundamental to health. One type of environmental stress that affects human cells is oxidative stress, which results from the production of reactive oxygen species during aerobic respiration or as a byproduct of thermal stress. Oxidative stress has been shown to cause human neurodegenerative diseases, such as Parkinson's and Alzheimer's, as well as the general phenomenon of aging. However, we do not know how oxidative stress affects cellular physiology and thereby causes the basis of these disease pathologies. The proposed research will contribute to our basic understanding of how cells experience environmental stress, what cellular components are most affected, and how cells maintain healthy function in the presence of stress. Our findings will provide candidate pathways that can be investigated toward the future development of treatments.